present invention relates to a diagnostic test procedure for detecting the active status of a noninfectious inflammatory condition such as interstitial cystitis.
Interstitial cystitis (IC) is a chronic debilitating inflammatory disorder of the bladder. The disease is most common in women ranging in age from about thirty to sixty with onset of the condition typically occurring at about forty years of age. The most prevalent symptoms include severe abdominal pain and urinary urgency two or three times per hour, day and night. The initiating causes are unknown and there is no known cure although alleviation of the symptoms can be obtained from selected treatment such as the use of dimethyl sulfoxide (DMSO). The condition is categorized as "interstitial cystitis" because it is believed the disease does not affect the surface of the bladder but instead involves the spaces between the cells, namely the interstices, in the lining of the bladder. Studies have indicated interstitial cystitis is not an auto-immune disease and no evidence exists that it is caused by infectious agents such as aerobic or anaerobic bacteria, viruses and the like. Accordingly, diagnosis is very difficult and treatments have met with limited success.
It has been found that even a cystoscopic examination, which is the insertion of a long thin viewing instrument into the bladder, will not lead with certainty to a diagnosis. Diagnosis using biochemical and laboratory test also have not proved to be extremely helpful. A urine culture can be taken to determine if a bacterial infection is present and thereby rule out other diseases. If no infection or disease is found, a hydrodistentive cystoscopic examination can be carried out under anesthesia. In this procedure the bladder is stretched by filling it with irrigating fluid and the bladder wall is carefully examined cystoscopically. This is the only known way of detecting the characteristic mucosal abnormalities associated with interstitial cystitis, namely the tiny hemorrhages and scar tissue on the bladder wall. Since diagnosis can be uncertain even when using this highly invasive hydrodistention technique, other factors such as case history, urine analysis and culture, bladder biopsy and response to therapy all must also be taken into consideration for a proper diagnosis.
In accordance with the present invention, it has been found that noninfectious inflammatory disorders, such as interstitial cystitis, can be diagnosed in a far less invasive manner with a high degree of accuracy through the utilization of the diagnostic procedure of the present invention. More specifically, this diagnostic procedure is capable of detecting the active inflammatory status of the tissue, including that caused by interstitial cystitis and other inflammatory disorders, through the simple detection of an inflammatory marker in fluid exposed to the inflamed tissue. Advantageously, the procedure will provide not only positive results during inflammation but also a negative test result when the condition is in remission, thereby adding to the specificity of the diagnostic procedure. It will, accordingly, be understood that the diagnostic procedure results in an indication of an active inflammatory condition rather than a determination of the presence in its passive state or absence of a particular disorder.
These and related advantages are achieved in accordance with the present invention by assaying fluids that have been in contact with the inflamed tissue, such as urine samples, or where necessary, by assaying urinary bladder biopsy specimens for the presence or absence of inflammatory mediators such as neutrophil chemotactic factors that stimulate the migration of neutrophils into sites of tissue damage.
In accordance with the present invention, it is believed that the inflammatory condition, such as occurs in interstitial cystitis, is accompanied by the release of inflammatory mediators that attract neutrophils. These neutrophil chemoattractants differ in their biochemical characteristics and molecular weight from previously known low molecular weight factors such as immune cell derived interleukin-1 or leukotriene B.sub.4. In accordance with the present invention, it has been found that neutrophil chemotactic factors (NCFs) are present in fluids exposed to the inner wall of the urinary bladder, such as urine, and by assaying the urine sample for the presence of neutrophil chemotactic factors it is possible to determine whether an active state of inflammation exists. The presence of the neutrophil chemotactic factors permits the isolation of antibodies specific for those chemotactic factors. Neutrophil chemotactic factors found in a variety of tissues and in various species are tissue specific and capable of signalling the initial inflammatory condition of the tissue to stimulate neutrophil migration to the inflamed area. Thus, the identification of the presence of the neutrophil chemotactic factors in the urine sample or bladder biopsy specimen provides a positive indication of the condition and a non-invasive diagnostic technique for detecting an active interstitial cystitis condition.